Natural resistance to HIV infection: lessons learned from HIV‐exposed uninfected individuals.

We explored potential mechanisms of resistance to human immunodeficiency virus type 1 (HIV‐1) infection in different groups of uninfected individuals exposed by systemic or mucosal routes: intravascular drug users in Vietnam and spouses of HIV‐infected individuals in Cambodia and Central African Republic. Our main findings were reduced susceptibility of peripheral blood mononuclear cells to HIV‐1 infection in vitro, associated with low levels of CD4+ T cell activation in vivo and/or cell restriction of viral replication, and enhanced natural killer cell activity, associated with increased ratios of activating to inhibitory natural killer cell receptors. These results support a contribution of innate responses to resistance against HIV‐1 infection. Scientific and ethical issues encountered during research in exposed uninfected subjects must be considered.